tbuckley/cabot-search huggingface dataset:
When the infectious environment meets the AD brain
Authors: Tal Ganz, Nina Fainstein, Tamir Ben-Hur
Journal: Molecular Neurodegeneration (2022)

Abstract Background The Amyloid theory of Alzheimer’s disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors. The infectious theory linked various infectious agents with the development of AD, raising the possibility that they serve as etiological causes of the disease. Are these theories mutually exclusive, or do they coincide? Main body In this review, we will discuss how the two theories converge. We present a model by which (1) the systemic infectious burden accelerates the development of AD brain pathology via bacterial Amyloids and other pathogen-associated molecular patterns (PAMPs), and (2) the developing AD brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived PAMPs, which drive neurodegeneration via activated microglia. Conclusions The reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling Alzheimer’s disease pathogenesis.
Delivery of DNA octahedra enhanced by focused ultrasound with microbubbles for glioma therapy
Authors: Yuanyuan Shen, Mengni Hu, Wen Li, Yiling Chen, Yiluo Xu, Litao Sun, Dongzhe Liu, Siping Chen, Yueqing Gu, Yi Ma, Xin Chen
Journal: Journal of Controlled Release (2022)
A Multicommunity Trial for Primary Prevention of Adolescent Drug Abuse
Authors: Mary Ann Pentz
Journal: JAMA (1989)

The entire early adolescent population of the 15 communities that constitute the Kansas City (Kansas and Missouri) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984. The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project, a longitudinal trial for primary prevention of cigarette, alcohol, and marijuana use in adolescents. The project includes mass media programming, a school-based educational program for youths, parent education and organization, community organization, and health policy components that are introduced sequentially into communities during a 6-year period. Effects of the program are determined through annual assessments of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions. In the first 2 years of the project, 22 500 sixth- and seventh-grade adolescents received the school-based educational program component, with parental involvement in homework and mass media coverage. Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition, with or without controlling for race, grade, socioeconomic status, and urbanicity (17% vs 24% for cigarette smoking, 11% vs 16% for alcohol use, and 7% vs 10% for marijuana use in the last month), and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools. (<i>JAMA</i>. 1989;261:3259-3266)
Development and Validation of a Model for Laparoscopic Colorectal Surgical Instrument Recognition Using Convolutional Neural Network–Based Instance Segmentation and Videos of Laparoscopic Procedures
Authors: Daichi Kitaguchi, Younae Lee, Kazuyuki Hayashi, Kei Nakajima, Shigehiro Kojima, Hiro Hasegawa, Nobuyoshi Takeshita, Kensaku Mori, Masaaki Ito
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Deep learning–based automatic surgical instrument recognition is an indispensable technology for surgical research and development. However, pixel-level recognition with high accuracy is required to make it suitable for surgical automation. <h3>Objective</h3> To develop a deep learning model that can simultaneously recognize 8 types of surgical instruments frequently used in laparoscopic colorectal operations and evaluate its recognition performance. <h3>Design, Setting, and Participants</h3> This quality improvement study was conducted at a single institution with a multi-institutional data set. Laparoscopic colorectal surgical videos recorded between April 1, 2009, and December 31, 2021, were included in the video data set. Deep learning–based instance segmentation, an image recognition approach that recognizes each object individually and pixel by pixel instead of roughly enclosing with a bounding box, was performed for 8 types of surgical instruments. <h3>Main Outcomes and Measures</h3> Average precision, calculated from the area under the precision-recall curve, was used as an evaluation metric. The average precision represents the number of instances of true-positive, false-positive, and false-negative results, and the mean average precision value for 8 types of surgical instruments was calculated. Five-fold cross-validation was used as the validation method. The annotation data set was split into 5 segments, of which 4 were used for training and the remainder for validation. The data set was split at the per-case level instead of the per-frame level; thus, the images extracted from an intraoperative video in the training set never appeared in the validation set. Validation was performed for all 5 validation sets, and the average mean average precision was calculated. <h3>Results</h3> In total, 337 laparoscopic colorectal surgical videos were used. Pixel-by-pixel annotation was manually performed for 81 760 labels on 38 628 static images, constituting the annotation data set. The mean average precisions of the instance segmentation for surgical instruments were 90.9% for 3 instruments, 90.3% for 4 instruments, 91.6% for 6 instruments, and 91.8% for 8 instruments. <h3>Conclusions and Relevance</h3> A deep learning–based instance segmentation model that simultaneously recognizes 8 types of surgical instruments with high accuracy was successfully developed. The accuracy was maintained even when the number of types of surgical instruments increased. This model can be applied to surgical innovations, such as intraoperative navigation and surgical automation.
Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer’s disease
Authors: Larissa Traxler, Joseph R. Herdy, Davide Stefanoni, Sophie Eichhorner, Silvia Pelucchi, Attila Szücs, Alice Santagostino, Yongsung Kim, Ravi K. Agarwal, Johannes C.M. Schlachetzki, Christopher K. Glass, Jessica Lagerwall, Douglas Galasko, Fred H. Gage, Angelo D’Alessandro, Jerome Mertens
Journal: Cell Metabolism (2022)

The drivers of sporadic Alzheimer's disease (AD) remain incompletely understood. Utilizing directly converted induced neurons (iNs) from AD-patient-derived fibroblasts, we identified a metabolic switch to aerobic glycolysis in AD iNs. Pathological isoform switching of the glycolytic enzyme pyruvate kinase M (PKM) toward the cancer-associated PKM2 isoform conferred metabolic and transcriptional changes in AD iNs. These alterations occurred via PKM2's lack of metabolic activity and via nuclear translocation and association with STAT3 and HIF1α to promote neuronal fate loss and vulnerability. Chemical modulation of PKM2 prevented nuclear translocation, restored a mature neuronal metabolism, reversed AD-specific gene expression changes, and re-activated neuronal resilience against cell death.
Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants
Authors: Michelle R. Asbury, Sara Shama, Jong Yup Sa, Nicole Bando, James Butcher, Elena M. Comelli, Julia K. Copeland, Victoria Forte, Alex Kiss, Philip M. Sherman, Alain Stintzi, Amel Taibi, Christopher Tomlinson, Sharon Unger, Pauline W. Wang, Deborah L. O’Connor
Journal: Cell Host & Microbe (2022)
A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis
Authors: Ying Xi, Ryan LaCanna, Hsiao-Yen Ma, Elsa-Noah N’Diaye, Sarah Gierke, Patrick Caplazi, Meredith Sagolla, Zhiyu Huang, Laura Lucio, Alexander Arlantico, Surinder Jeet, Hans Brightbill, Claire Emson, Aaron Wong, Katrina B. Morshead, Daryle J. DePianto, Merone Roose-Girma, Charles Yu, Lucinda Tam, Guiquan Jia, Thirumalai R. Ramalingam, Scot Marsters, Avi Ashkenazi, Si Hyun Kim, Ryan Kelly, Shuang Wu, Paul J. Wolters, Ariel E. Feldstein, Jason A. Vander Heiden, Ning Ding
Journal: Cell Metabolism (2022)
Continuous Glucose Monitoring–Guided Insulin Administration in Hospitalized Patients With Diabetes: A Randomized Clinical Trial
Authors: Elias K. Spanakis, Agustina Urrutia, Rodolfo J. Galindo, Priyathama Vellanki, Alexandra L. Migdal, Georgia Davis, Maya Fayfman, Thaer Idrees, Francisco J. Pasquel, Walkiria Zamudio Coronado, Bonnie Albury, Emmenlin Moreno, Lakshmi G. Singh, Isabel Marcano, Sergio Lizama, Chikara Gothong, Kashif Munir, Catalina Chesney, Rebecca Maguire, William H. Scott, M. Citlalli Perez-Guzman, Saumeth Cardona, Limin Peng, Guillermo E. Umpierrez
Journal: Diabetes Care (2022)

The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated.This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70-180 mg/dL) and hypoglycemia (<70 mg/dL and <54 mg/dL).There were no significant differences in TIR (54.51% ± 27.72 vs. 48.64% ± 24.25; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values <70 mg/dL (36% vs. 39%; P = 0.68) or <54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range <70 mg/dL (1.89% ± 3.27 vs. 5.47% ± 8.49; P = 0.02), and lower incidence rate ratio <70 mg/dL (0.53 [95% CI 0.31-0.92]) and <54 mg/dL (0.37 [95% CI 0.17-0.83]).The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.
First case of monkeypox virus, SARS-CoV-2 and HIV co-infection
Authors: Santi Nolasco, Francesco Vitale, Alessandro Geremia, Fabio Tramuto, Carmelo Massimo Maida, Alice Sciuto, Christian Coco, Rosa Manuele, Emilio Frasca, Maria Frasca, Salvatore Magliocco, Alfio Gennaro, Elda Tumino, Mauro Maresca, Arturo Montineri
Journal: Journal of Infection (2022)
Associations of New-Onset Atrial Fibrillation With Risks of Cardiovascular Disease, Chronic Kidney Disease, and Mortality Among Patients With Type 2 Diabetes
Authors: Tingting Geng, Yi Wang, Qi Lu, Yan-Bo Zhang, Jun-Xiang Chen, Yan-Feng Zhou, Zhenzhen Wan, Kunquan Guo, Kun Yang, Liegang Liu, Gang Liu, An Pan
Journal: Diabetes Care (2022)

OBJECTIVE Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. RESEARCH DESIGN AND METHODS We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. RESULTS Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7–11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59–2.16), heart failure (HR 4.40; 95% CI 3.67–5.28), CKD (HR 1.68; 95% CI 1.41–2.01), all-cause mortality (HR 2.91; 95% CI 2.53–3.34), and CVD mortality (HR 3.75; 95% CI 2.93–4.80) compared with those without incident AF. CONCLUSIONS Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.
Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis
Authors: Mingyue Cheng, Yan Zhao, Yazhou Cui, Chaofang Zhong, Yuguo Zha, Shufeng Li, Guangxiang Cao, Mian Li, Lei Zhang, Kang Ning, Jinxiang Han
Journal: Annals of the Rheumatic Diseases (2022)

Rheumatoid arthritis (RA) is a progressive disease including four stages, where gut microbiome is associated with pathogenesis. We aimed to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in RA.
Dietary methionine starvation impairs acute myeloid leukemia progression
Authors: Alan Cunningham, Ayşegül Erdem, Islam Alshamleh, Marjan Geugien, Maurien Pruis, Diego Antonio Pereira-Martins, Fiona A. J. van den Heuvel, Albertus T. J. Wierenga, Hilde ten Berge, Robin Dennebos, Vincent van den Boom, Shanna M. Hogeling, Isabel Weinhäuser, Ruth Knops, Pim de Blaauw, M. Rebecca Heiner-Fokkema, Carolien Woolthuis, Ulrich L. Günther, Eduardo M. Rego, Joost H. A. Martens, Joop H. Jansen, Harald Schwalbe, Gerwin Huls, Jan Jacob Schuringa
Journal: Blood (2022)
Reply to R. Sun et al
Authors: Andrew J. Armstrong, Brad Rosbrook, Shunsuke Yamada
Journal: Journal of Clinical Oncology (2022)

We recently published results from the final prespecified analysis of overall survival (OS) in the ARCHES trial, a phase III, double-blind study of enzalutamide (160 mg once daily) plus androgen deprivation therapy (ADT) versus placebo plus ADT. 1 In that analysis, enzalutamide plus ADT demonstrated a clinically meaningful and statistically significant increase in OS compared with placebo plus ADT (hazard ratio [HR], 0.66; 95% CI, 0.53 to 0.81; log-rank P , .001).Sun and Wei 2 have raised concerns about the use and interpretation of the HR for the OS end point and a lack of median Kaplan-Meier (KM) estimates from the data.They note that the validity of the HR depends on a proportional hazards assumption and suggest that this assumption is likely invalid.In our analysis, we considered the proportional hazards assumption to be appropriate, as observed by a visual examination of the log-log plot and the Kolmogorov-type supremum test (P 5 .4440).Furthermore, the HR is not the sole descriptor of treatment effect presented; we also presented the KM curve and provided KM estimates at 24, 36, and 48 months. 1 The HR is appropriate for these data and supported by the summaries of the KM curves and by the log-rank test; the KM curves and logrank test do not require proportional hazards assumptions and are independent of the Cox HR.These statistics are clinically meaningful to clinicians and well-understood by the scientific community.
Abstract 13540: Non-Invasive Quantitative Assessment of Coronary Flow Reserve Improves Cardiac Risk Assessment in Patients with Diabetes
Authors: Venkatesh L Murthy, Masanao Naya, Courtney R Foster, Mariya Gaber, Hainer Jon, Sharmila Dorbala, Arkadiusz Sitek, Marcelo Di Carli
Journal: Circulation (2011)

Objectives: To evaluate the incremental prognostic value of quantitative coronary flow reserve (CFR) measured by positron emission tomography (PET) in patients with diabetes and known or suspected ...
Generation of realistic synthetic data using Multimodal Neural Ordinary Differential Equations
Authors: Philipp Wendland, Colin Birkenbihl, Marc Gomez-Freixa, Meemansa Sood, Maik Kschischo, Holger Fröhlich
Journal: npj Digital Medicine (2022)

Individual organizations, such as hospitals, pharmaceutical companies, and health insurance providers, are currently limited in their ability to collect data that are fully representative of a disease population. This can, in turn, negatively impact the generalization ability of statistical models and scientific insights. However, sharing data across different organizations is highly restricted by legal regulations. While federated data access concepts exist, they are technically and organizationally difficult to realize. An alternative approach would be to exchange synthetic patient data instead. In this work, we introduce the Multimodal Neural Ordinary Differential Equations (MultiNODEs), a hybrid, multimodal AI approach, which allows for generating highly realistic synthetic patient trajectories on a continuous time scale, hence enabling smooth interpolation and extrapolation of clinical studies. Our proposed method can integrate both static and longitudinal data, and implicitly handles missing values. We demonstrate the capabilities of MultiNODEs by applying them to real patient-level data from two independent clinical studies and simulated epidemiological data of an infectious disease.
High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month
Authors: Chang Xie, Renjie Liang, Jinchun Ye, Zhi Peng, Heng Sun, Qiuwen Zhu, Xilin Shen, Yi Hong, Hongwei Wu, Wei Sun, Xudong Yao, Jiajin Li, Shufang Zhang, Xianzhu Zhang, Hongwei Ouyang
Journal: Biomaterials (2022)
23rd Congress of the European Hematology Association Stockholm, Sweden, June 14‐17, 2018
Journal: HemaSphere (2018)

This is an open access Abstract Book distributed under the Attribution-NonCommercial-NoDerivs (CCBY-NC-ND), which allows third parties to download the abstracts and share them with others as long as they credit the author and the abstract book, but they cannot change the content in any way or use them commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
A Manual of the Treatment of Fractures
Journal: JAMA (1942)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cardiac Fibroblast
Authors: Colby A. Souders, Stephanie L.K. Bowers, Troy A. Baudino
Journal: Circulation Research (2009)

The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells, and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell–cell communication with myocytes, cell–cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. Although a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review, we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart.
Patient Characteristics and Survival for Progressive Pulmonary Fibrosis Using Different Definitions
Authors: Yet H. Khor, Malik Farooqi, Nathan Hambly, Martin Kolb, Christopher J. Ryerson, Deborah Assayag, Gerard Cox, Charlene D. Fell, Jolene H. Fisher, Andrea S. Gershon, Nicole Goh, Andrew J. Halayko, Kerri A. Johannson, Nasreen Khalil, Stacey Lok, Helene Manganas, Veronica Marcoux, Julie Morisset, Mohsen Sadatsafavi, Shane Shapera, Teresa To, Pearce G. Wilcox, Alyson W. Wong
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
miR-196b–TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in <i>DNMT3A</i>-Mutant AML
Authors: Holly A. Gamlen, Jennifer S. Romer-Seibert, Michael E. Lawler, Amanda M. Versace, Melanie L. Goetz, Yang Feng, Olga A. Guryanova, Neil Palmisiano, Sara E. Meyer
Journal: Clinical Cancer Research (2022)

Abstract Purpose: DNMT3A mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of DNMT3A mutations in disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role of miRNA in DNMT3A-mutant AML pathogenesis is understudied. Experimental Design: DNA methylation and miRNA expression was evaluated in human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. The treatment efficacy and molecular mechanisms of TLR7/8-directed therapies on DNMT3A-mutant AML were evaluated in vitro on human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. Results: miR-196b is hypomethylated and overexpressed in DNMT3A-mutant AML and is associated with poor patient outcome. miR-196b overexpression in DNMT3A-mutant AML is important to maintain an immature state and leukemic cell survival through repression of TLR signaling. The TLR7/8 agonist resiquimod induces dendritic cell–like differentiation with costimulatory molecule expression in DNMT3A-mutant AML cells and provides a survival benefit to Dnmt3a/Flt3-mutant AML mice. The small molecule bryostatin-1 augments resiquimod-mediated AML growth inhibition and differentiation. Conclusions: DNMT3A loss-of-function mutations cause miRNA locus-specific hypomethylation and overexpression important for mutant DNMT3A–mediated pathogenesis and clinical outcomes. Specifically, the overexpression of miR-196b in DNMT3A-mutant AML creates a novel therapeutic vulnerability by controlling sensitivity to TLR7/8-directed therapies.